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Medical treatment of Parkinsonism

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

NICE guidance suggests (1)

First-line treatment (1)

  • levodopa should be offered to people in the early stages of Parkinson's disease whose motor symptoms impact on their quality of life
  • for people in the early stages of Parkinson's disease whose motor symptoms do not impact on their quality of life
    • consider a choice of dopamine agonists, levodopa or monoamine oxidase B (MAO-B) inhibitors
    • do not offer ergot-derived dopamine agonists as first-line treatment for Parkinson's disease

Adjuvant treatment of motor symptoms

  • if a person with Parkinson's disease has developed dyskinesia and/or motor fluctuations, including medicines 'wearing off', seek advice from a healthcare professional with specialist expertise in Parkinson's disease before modifying therapy
  • a choice of dopamine agonists, MAO-B inhibitors or catechol-O-methyl transferase (COMT) inhibitors should be offered as an adjunct to levodopa for people with Parkinson's disease who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy, after discussing:
    • person's individual clinical circumstances, for example, their Parkinson's disease symptoms, comorbidities and risks from polypharmacy
    • person's individual lifestyle circumstances, preferences, needs and goals
    • potential benefits and harms of the different drug classes

Dopamine agonists

MAO-B inhibitors

COMT inhibitors

Amantadine

Motor symptoms

amelioration in motor symptoms

amelioration in motor symptoms

amelioration in motor symptoms

No evidence of amelioration in motor symptoms

Activities of daily living

amelioration in activities of daily living

amelioration in activities of daily living

amelioration in activities of daily living

No evidence of amelioration in activities of daily living

Off time

More off-time reduction

Off-time reduction

Off-time reduction

No studies reporting this outcome

Adverse events

Intermediate risk of adverse events

Fewer adverse events

More adverse events

No studies reporting this outcome

Hallucinations

More risk of hallucinations

Lower risk of hallucinations

Lower risk of hallucinations

No studies reporting this outcome

  • in most cases a non-ergot-derived dopamine agonist in most cases, because of the monitoring that is needed with ergot-derived dopamine agonists
    • an ergot-derived dopamine agonist should only be chosesn as an adjunct to levodopa for people with Parkinson's disease:
      • who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy and
      • whose symptoms are not adequately controlled with a non-ergot-derived dopamine agonist
  • amantadine should be considered if dyskinesia is not adequately managed by modifying existing therapy

The commonly used drugs in the management of Parkinson's disease are listed below:

  • L-dopa:
    • levodopa may be used as a symptomatic treatment for people with early PD (1)
    • first line treatment for most patients
      • offer levodopa to people in the early stages of Parkinson's disease whose motor symptoms impact on their quality of life (1)
    • usually combined with an inhibitor of peripheral dopa decarboxylase
    • slow-release preparations may reduce side-effects
    • the dose of levodopa should be kept as low as possible to maintain good function in
      order to reduce the development of motor complications (1)
    • a newer preparation of the drug has been licensed for the treatment of severe motor complications - a levedopa gel (Duodopa) used as a continuous infusion directly into the jejunum (2)

  • dopamine receptor (D2) agonists:
    • Dopamine agonists may be used as a symptomatic treatment for people with early PD (1)
    • considered a possible first line treatment (1)
    • in advanced disease used in conjunction with L-dopa to control fluctuations in response and required levadopa dose (2)
    • may be used as monotherapy in early disease - it has been hypothesised that introducing dopamine agonists in the early stages of disease, before L-dopa
      • is useful in controlling the motor symptoms (although less effective than levadopa)
      • is associated with fewer motor complications compared to levadopa (2)
    • there are 2 groups
      • ergot-related - bromocriptine, cabergoline, lisuride and pergolide
      • non-ergot-related - ropinirole, pramipexole and rotigotine (2)
    • non ergot related drugs are used as first line treatment due to the associated risk of severe fibrotic and serosal inflammatory disorders seen with the ergot related preparations (2).
    • if an ergot-derived dopamine agonist is used, the patient should have a minimum of renal function tests, erythrocyte sedimentation rate (ESR) and chest radiograph performed before starting treatment, and annually thereafter (1)
    • ropinirole XL (once-daily) can be used in both the early and advanced disease (2)

  • MAOB (monamine oxidase type B) inhibitors e.g. selegiline, rasagiline:
    • inhibitors may be used as a symptomatic treatment for people with early PD (1)
    • the use of this drug class is controversial
    • may be used in advanced Parkinson's to reduce motor fluctuations (2)
    • considered a possible first-line therapy (1)


  • COMT-inhibition: e.g.- entacapone, tolcapone:
    • second line treatment
    • used as an adjunct to L-dopa (increases half life of the drug)

  • anticholinergic agents:
    • occasionally used especially when tremor predominates
    • may be used as a symptomatic treatment typically in young people with early PD and severe tremor
    • should not be drugs of first choice due to limited efficacy and the propensity to cause neuropsychiatric side effects

  • amantadine:
    • response rate is low and tolerance occurs
    • may be used as a treatment for people with early PD but should not be a drug of first choice
  • beta blockers
    • may be used in the symptomatic treatment of selected people with postural tremor in PD, but should not be drugs of first choice (1)

  • apomorphine
    • a potent dopamine agonist
    • useful in patients with severe motor complications to decrease 'off' periods and dyskinesia
    • currently two treatment approaches are used
      • in patients with less than six 'off' periods per day - intermittent subcutaneous rescue injections
      • in patients with more frequent episodes - continuous infusion (2)

 

Reference:

  1. NICE (July 2017). Parkinson's disease in adults
  2. Turnbull C, Fitzsimmons P. Advances in the treatment of the motor symptoms of Parkinson's disease. J R Coll Physicians Edinb 2009; 39:29-31
  3. MeReC Bulletin 1999;10 (10): 37-40.
  4. Parkinson's disease Research Group of the United Kingdom. Comparison of therapeutic effects and mortality data of levodopa and levodopa commbined with selegiline in patients with early, mild Parkinson's disease. BMJ 1995; 311: 1602-7.

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